PFKP deubiquitination and stabilization by USP5 activate aerobic glycolysis to promote triple-negative breast cancer progression.

BACKGROUND: Triple-negative breast cancer (TNBC) remains the most challenging subtype of breast cancer and lacks definite treatment targets. Aerobic glycolysis is a hallmark of metabolic reprogramming that contributes to cancer progression. PFKP is a rate-limiting enzyme involved in aerobic glycolysis, which is overexpressed in various types of cancers. However, the underlying mechanisms and roles of the posttranslational modification of PFKP in TNBC remain unknown. METHODS: To explore whether PFKP protein has a potential role in the progression of TNBC, protein levels of PFKP in TNBC and normal breast tissues were examined by CPTAC database analysis, immunohistochemistry staining (IHC), and western blotting assay. Further CCK-8 assay, colony formation assay, EDU incorporation assay, and tumor xenograft experiments were used to detect the effect of PFKP on TNBC progression. To clarify the role of the USP5-PFKP pathway in TNBC progression, ubiquitin assay, co-immunoprecipitation (Co-IP), mass spectrometry-based protein identification, western blotting assay, immunofluorescence microscopy, in vitro binding assay, and glycolysis assay were conducted. RESULTS: Herein, we showed that PFKP protein was highly expressed in TNBC, which was associated with TNBC progression and poor prognosis of patients. In addition, we demonstrated that PFKP depletion significantly inhibited the TNBC progression in vitro and in vivo. Importantly, we identified that PFKP was a bona fide target of deubiquitinase USP5, and the USP5-mediated deubiquitination and stabilization of PFKP were essential for cancer cell aerobic glycolysis and TNBC progression. Moreover, we found a strong positive correlation between the expression of USP5 and PFKP in TNBC samples. Notably, the high expression of USP5 and PFKP was significantly correlated with poor clinical outcomes. CONCLUSIONS: Our study established the USP5-PFKP axis as an important regulatory mechanism of TNBC progression and provided a rationale for future therapeutic interventions in the treatment of TNBC.

Chinese Experts Consensus and Practice Guideline on Discoid Lateral Meniscus.

Discoid lateral meniscus (DLM) is the most common congenital variant of the lateral meniscus, which is prone to degeneration and lesions, and often leads to knee osteoarthritis. At present, there is no consensus on the clinical practice of DLM, and this expert consensus and practice guidelines on DLM was developed and approved by Chinese Society of Sports Medicine according to the Delphi method. Among 32 statements drafted, 14 statements were excluded for redundant information, and 18 statements achieved consensus. This expert consensus focused on the definition, epidemiology, etiology, classification, clinical manifestations, diagnosis, treatment, prognosis, and rehabilitation of DLM. Restoring the normal shape, retaining appropriate width and thickness, and ensuring the stability of the remnant meniscus is critical to sustaining the physiological function of the meniscus and preserving the knee. The partial meniscectomy with or without repair should be the first-line treatment when possible, given that the clinical and radiological long-term outcomes of total or subtotal meniscectomy are worse.

Guidelines on the Diagnosis and Treatment of Lateral Meniscal Lesions: A Consensus Statement by the Chinese Society of Sports Medicine.

Background: The lateral meniscus is a unique structure of the knee joint, and its anatomy, function, pathological process, and treatment are distinct from those of the medial meniscus. To date, no consensus on the management of lateral meniscal lesions has been published, and clinical decision-making is challenging. To facilitate this, consensus and practice guidelines for lateral meniscal lesions were developed and endorsed by the Chinese Society of Sports Medicine. Study Design: Consensus statement. Methods: This project followed the Delphi approach to the consensus process, involving steering, rating, and peer review groups. A total of 61 experts in the fields of sports medicine and arthroscopic surgery were invited to participate in the compilation of a consensus statement on lateral meniscal lesions. (The discoid lateral meniscus was addressed by separate consensus.) To begin, the steering group drafted a set of questions and replies regarding lateral meniscal lesions. An online panel discussion was then held to provide initial agreement and comments on the statements, followed by a round of anonymous voting. Results and feedback were sent to the steering group for a second draft. A second round of voting was then held, and each statement was discussed during a combined meeting of the steering and rating groups. Finally, a consensus draft was evaluated by a review group. Results: Fifty-three questions and answers addressing lateral meniscal lesions were drafted, and 20 statements were excluded because of redundant information during the first round of voting. Ultimately, 33 statements were completed, 9 of which were unanimous. Conclusion: This expert consensus process focused on the anatomy, function, pathological processes, and treatment of lateral meniscal lesions. Accepted recommendations in these areas can assist doctors and therapists in standardizing the management of related pathology. The consensus statement indicates that certain types of lateral meniscal tears that were previously considered irreparable can be repaired. Preservation of the lateral meniscus should be the first-line treatment whenever possible, because the long-term clinical and radiological outcomes are worse after partial meniscectomy.

Traditional Chinese Acupressure Massage of the Quadriceps Femoris Can Relieve Flexion Pain after Undergoing Total Knee Arthroplasty.

Objective: To reduce the pain of quadriceps during knee flexion after total knee arthroplasty and increase range motion of knee flexion. Design: Three-month prospective before/after quality improvement project. Setting. Department of Bone and Joint Surgery. Participants. A total of 80 patients who met the surgical indications were admitted to the outpatient department for surgery. They were randomly grouped by computer in advance, and the patients were divided into two groups according to the time of admission, each with 40 cases. Intervention. The intervention group performed routine rehabilitation exercises and received quadriceps acupoint massages for 20 minutes twice a day for two consecutive weeks. The control group performed routine rehabilitation exercises, such as gentle quadriceps massage for 20 minutes twice a day for two consecutive weeks. Main Outcome Measures. PPT (pressure pain threshold) of quadriceps femoris/VAS (visual analog scale) of knee flexion and motion of knee flexion. Results: The VAS score, range of motion, and tenderness threshold during flexion were significantly better in the intervention group than in the control group at 1, 2, and 4 weeks after surgery. But the VAS score, range of motion, and tenderness threshold did not significantly differ between groups at 12 weeks after surgery. Conclusion: Acupoint massage of the quadriceps femoris can relieve early flexion pain in patients after total knee arthroplasty. The trial was registered at clinical trials.gov.

Mechanical mechanism of suture passer needle break in rotator cuff repair.

Introduction: Suture passer needle, as one of commonly used instrument in the arthroscopic rotator cuff repair, often breaks at the notch of the needle, which originally was designed to facilitate suture with thread. Our study aimed to evaluate the suture failure rate and stitch success rate between intact suture needle and broken needle and explore the mechanism of the needle breakage and achieving better future designs. Materials and methods: From 2017 to 2021, consecutive 437 shoulders (11 cases were bilateral) underwent arthroscopic repair for full-thickness rotator cuff tear at the authors' institution. The breakage of needles was recorded. Finite elements analysis and mechanical test were utilized to compare stress distribution, puncture performance, and loaded puncture performance between the broken needle and the intact needle. Results: We identified 19 consecutive patients for whom the needle tip of the TruePass™ suture passer was broken in the 437 shoulder surgeries. Based on the finite element analysis of Abaqus, around the tip and the notch of the intact needle was a large stress concentration. The average puncture force required by intact needle tip and the broken tip is 61.78N and 78.23N respectively. While the intact tip with notch is easier to break than the broken tip. Conclusions: The notch of the needle is a weak point in mechanics. The broken needle without the notch still has good tendon piercing and thread passing ability. The notch of needle may be not necessary, and the tip of the needle should be modified.

[Research progress about influence of patellofemoral osteoarthritis on effectiveness of unicompartmental knee arthroplasty].

Objective: To summarize the current research progress about influence of patellofemoral osteoarthritis on clinical outcome of unicompartmental knee arthroplasty (UKA). Methods: The recent related literature was extensively reviewed and summarized, including pros and cons to regard the patellofemoral osteoarthritis as the contraindication. Results: Previous studies regarded patellofemoral osteoarthritis as the contraindication of UKA. Most of current researches show that the damage to the articular cartilage of the patellofemoral joint to the extent of full-thickness cartilage loss has no influence on outcome of UKA. There is no correlation between preoperative anterior knee pain or medial patellofemoral joint degeneration and the clinical outcome. However, lateral subluxation of the patella has an adverse impact on postoperative curative effect. Degeneration of the lateral patellofemoral joint may be a risk factor of the outcome. Conclusion: Patellofemoral osteoarthritis should not be the absolute contraindication of UKA. The effect of degeneration of the lateral patellofemoral joint is not clear at present, and still needs further studies in the future.

Disruption of Quorum Sensing and Virulence in Burkholderia cenocepacia by a Structural Analogue of the cis-2-Dodecenoic Acid Signal.

Quorum sensing (QS) signals are widely used by bacterial pathogens to control biological functions and virulence in response to changes in cell population densities. Burkholderia cenocepacia employs a molecular mechanism in which the cis-2-dodecenoic acid (named Burkholderiadiffusible signal factor [BDSF]) QS system regulates N-acyl homoserine lactone (AHL) signal production and virulence by modulating intracellular levels of cyclic diguanosine monophosphate (c-di-GMP). Thus, inhibition of BDSF signaling may offer a non-antibiotic-based therapeutic strategy against BDSF-regulated bacterial infections. In this study, we report the synthesis of small-molecule mimics of the BDSF signal and evaluate their ability to inhibit BDSF QS signaling in B. cenocepacia A novel structural analogue of BDSF, 14-Me-C16:Δ2 (cis-14-methylpentadec-2-enoic acid), was observed to inhibit BDSF production and impair BDSF-regulated phenotypes in B. cenocepacia, including motility, biofilm formation, and virulence, while it did not inhibit the growth rate of this pathogen. 14-Me-C16:Δ2 also reduced AHL signal production. Genetic and biochemical analyses showed that 14-Me-C16:Δ2 inhibited the production of the BDSF and AHL signals by decreasing the expression of their synthase-encoding genes. Notably, 14-Me-C16:Δ2 attenuated BDSF-regulated phenotypes in various Burkholderia species. These findings suggest that 14-Me-C16:Δ2 could potentially be developed as a new therapeutic agent against pathogenic Burkholderia species by interfering with their QS signaling.IMPORTANCEBurkholderia cenocepacia is an important opportunistic pathogen which can cause life-threatening infections in susceptible individuals, particularly in cystic fibrosis and immunocompromised patients. It usually employs two types of quorum sensing (QS) systems, including the cis-2-dodecenoic acid (BDSF) system and N-acyl homoserine lactone (AHL) system, to regulate virulence. In this study, we have designed and identified an unsaturated fatty acid compound (cis-14-methylpentadec-2-enoic acid [14-Me-C16:Δ2]) that is capable of interfering with B. cenocepacia QS signaling and virulence. We demonstrate that 14-Me-C16:Δ2 reduced BDSF and AHL signal production in B. cenocepacia It also impaired QS-regulated phenotypes in various Burkholderia species. These results suggest that 14-Me-C16:Δ2 could interfere with QS signaling in many Burkholderia species and might be developed as a new antibacterial agent.

Alamandine injected into the paraventricular nucleus increases blood pressure and sympathetic activation in spontaneously hypertensive rats.

Alamandine is a newly discovered new component of the renin-angiotensin (Ang) system (RAS) that has been shown to exert vasoactive effects in some areas of the nervous system. The present study investigated whether administration of alamandine to the hypothalamic paraventricular nucleus (PVN) modulates blood pressure and sympathetic activity. Mean arterial pressure (MAP) and renal sympathetic nerve activity (RSNA) were recorded in anaesthetized rats. PVN microinjection of alamandine increased MAP and RSNA both in Wistar-Kyoto (WKY) rats and in spontaneously hypertensive rats (SHRs), but to a greater extent in SHRs. Moreover, these effects were blocked by pretreatment with alamandine receptor Mas-related G-protein-coupled receptor, member D (MrgD) antagonist D-Pro7-Ang-(1-7), adenylyl cyclase (AC) inhibitor SQ22536, and protein kinase A (PKA) inhibitor rp-adenosine-3',5'-cyclic monophosphorothionate (Rp-cAMP). Treatment with D-Pro7-Ang-(1-7), SQ22536, or Rp-cAMP alone in PVN decreased MAP and RSNA in the SHRs. Conversely cAMP alone increased MAP and RSNA, and pretreatment with cAMP enhanced alamandine's effects. These results indicate that microinjection of alamandine into the PVN increases blood pressure and sympathetic outflow via MrgD and the cAMP-PKA pathway.

High magnesium prevents matrix vesicle-mediated mineralization in human bone marrow-derived mesenchymal stem cells via mitochondrial pathway and autophagy.

Magnesium, as a physiological calcium antagonist, plays a vital role in the bone metabolism and the balance between magnesium and calcium is crucial in bone physiology. We recently demonstrated that matrix mineralization in human bone marrow-derived mesenchymal stem cells (hBMSCs) can be suppressed by high Mg2+ . However, a complete understanding of the mechanisms involved still remains to be elucidated. As mitochondrial calcium phosphate granules depletion manifests concurrently with the appearance of matrix vesicles (MVs) and autophagy are associated with matrix mineralization, we studied the effect of high extracellular Mg2+ on these pathways. Our results first demonstrated that high Mg2+ has a significant inhibitory effect on the generalization of extracellular mineral aggregates and the expression of collagen 1 along which the mineral crystals grow. Transmission electron microscope results showed that less amount of MVs were observed inside hBMSCs treated with high Mg2+ and high Mg2+ inhibited the release of MVs. In addition, high Mg2+ significantly suppressed mitochondrial Ca2+ accumulation. Autophagy is promoted as a response to osteogenesis of hBMSCs. High Mg2+ inhibited the level of autophagy upon osteogenesis and autophagy inhibitor 3-MA significantly suppressed mineralization. Exogenous ATP can reverse the inhibitory effect of high Mg2+ by increasing the level of autophagy. Taken together, our results indicate that high Mg2+ may modulate MVs-mediated mineralization via suppressing mitochondrial Ca2+ intensity and regulates autophagy of hBMSCs upon osteogenesis, resulting in decreased extracellular mineralized matrix deposition. Our results contribute to the understanding of the role of magnesium homeostasis in osteoporosis and the design of magnesium alloys.

[RESEARCH PROGRESS OF THREE-DIMENSIONAL PRINTING POROUS SCAFFOLDS FOR BONE TISSUE ENGINEERING].

OBJECTIVE: To summarize the research progress of several three-dimensional (3-D)-printing scaffold materials in bone tissue engineering. METHODS: The recent domestic and international articles about 3-D printing scaffold materials were reviewed and summarized. RESULTS: Compared with conventional manufacturing methods, 3-D printing has distinctive advantages, such as enhancing the controllability of the structure and increasing the productivity. In addition to the traditional metal and ceramic scaffolds, 3-D printing scaffolds carrying seeding cells and tissue factors as well as scaffolds filling particular drugs for special need have been paid more and more attention. CONCLUSION: The development of 3-D printing porous scaffolds have revealed new perspectives in bone repairing. But it is still at the initial stage, more basic and clinical researches are still needed.

Magnesium inhibits the calcification of the extracellular matrix in tendon-derived stem cells via the ATP-P2R and mitochondrial pathways.

Tendon calcification has been widely regarded by researchers to result from the osteogenic differentiation of Tendon-Derived Stem Cells (TDSCs) and ectopic mineralization caused by the calcification of cellular matrix. Recent studies have revealed a correlation between the Mg(2+)/Ca(2+) balance and the degeneration or calcification of tendon tissues. Furthermore, the ATP-P2X/P2Y receptor pathway has been shown to play a decisive role in the process of calcification, with calcium exportation from mitochondria and calcium oscillations potentially representing the cohesive signal produced by this pathway. Our previous study demonstrated that matrix calcification is inhibited by magnesium. In this study, we examined the effects of extracellular Mg(2+) on the deposition of calcium phosphate matrix and cellular pathways in TDSCs. The suppression of the export of calcium from mitochondria has also been detected. We found that a high concentration of extracellular Mg(2+) ([Mg(2+)]e) inhibited the mineralization of the extracellular matrix in TDSCs and that 100 µM ATP reversed this inhibitory effect in vitro. In addition, the spontaneous release of ATP was inhibited by high [Mg(2+)]e levels. A high [Mg(2+)]e suppressed the expression of P2X4, P2X5 and P2X7 and activated the expression of P2Y1, P2Y2, P2Y4 and P2Y14. The interaction between Mg(2+) and Ca(2+) is therefore contradictory, Mg(2+) inhibits mitochondrial calcium concentrations, meanwhile it reverses the opening of mPTP that is induced by Ca(2+). JC-1 staining verified the protective effect of Mg(2+) on mitochondrial membrane potential and the decrease induced by Ca(2+). Taken together, these results indicate that high [Mg(2+)]e interferes with the expression of P2 receptors, resulting in decreased extracellular mineralization. The balance between Mg(2+) and Ca(2+) influences mitochondrial calcium exportation and provides another explanation for the mechanism underlying matrix calcification in TDSCs.

A new method to diagnose discoid lateral menisci on radiographs.

PURPOSE: The aim of this study was to prove that it is feasible to diagnose discoid lateral meniscus in radiographs. Plain radiographic findings of discoid lateral menisci with matched controls were analysed and compared in a quantitative method. METHODS: Sixty consecutive patients (60 knees) who were diagnosed with discoid lateral meniscus (discoid group) by magnetic resonance imaging (MRI) were included. Another 60 age- and sex-matched controls with normal medial and lateral menisci on the basis of MRI findings were included as the control group. Each plain radiograph was evaluated from the anteroposterior view for the following variables: height of the fibular head (HFH), lateral joint space distance (LJSD), height of the lateral tibial spine (HLTS), obliquity of the lateral tibial plateau, obliquity of the lateral femoral condyle, distance from the lateral tibial spine to the lateral femoral condyle, height of the medial tibial spine, chordal distance of the femoral condyle (CDLF, CDMF), the HFH/LJSD, LJSD/HLTS and the CDLF/CDMF. RESULTS: A significant difference was found in the HFH, LJSD, HLTS, DLC, CDLF, HFH/LJSD and LJSD/HLTS between the two groups. The cut-off values of the HFH, LJSD, HLTS, DLC, CDLF, HFH/LJSD and LJSD/HLTS were 12.9 mm, 6.6 mm, 7.8 mm, 3.0 mm, 2.7 mm, 2.0 and 0.9, respectively. Among the cut-off values in diagnosing discoid lateral meniscus, the sensitivity, specificity and ROC curve area of LJSD/HLTS were as high as 73.6 %, 83.0 % and 0.8, respectively. The corresponding values of the HFH/LJSD were as high as 66.0 %, 86.8 % and 0.8. For the first two indicators, the results of the HFH/LJSD and LJSD/HLTS were higher than that of most other parameters. At the same time, the ROC curve area of the HFH/LJSD and LJSD/HLTS ranked highest among all the results. CONCLUSION: There were significant differences in the HFH, LJSD, HLTS, DLC, CDLF, HFH/LJSD and LJSD/HLTS, especially the HFH/LJSD and the LJSD/HLTS, between plain radiographic findings of discoid lateral meniscus patients and normal controls. The results of the HFH/LJSD and the LJSD/HLTS showed a positive impact on the diagnosis of discoid lateral meniscus in this research. These findings enable radiographs to screen for discoid lateral meniscus. LEVEL OF EVIDENCE: II.

[RESEARCH PROGRESS OF OSTEOTOMY IN TOTAL HIP ARTHROPLASTY TO TREAT CROWE TYPE IV DEVELOPMENTAL DYSPLASIA OF THE HIP].

OBJECTIVE: To summarize the methods and complications of osteotomy in total hip arthroplasty (THA) to treat Crowe type IV developmental dysplasia of the hip (DDH) so as to provide the reference for selection of surgical procedures. METHODS: The literature concerning THA for DDH was reviewed, and the effectiveness and complications were summarized in different methods. RESULTS: At present, four osteotomies are commonly used in DDH, including transtrochanteric osteotomy, subtrochanteric osteotomy, lesser trochanteric osteotomy, and distal femoral osteotomy. Transtrochanteric osteotomy and subtrochanteric osteotomy can effectively adjust leg length, correct femoral anteversion and avoid nerve injury, but transtrochanteric osteotomy may cause bone fracture and abductor injury. Lesser trochanteric osteotomy is scarcely used because of its poor effectiveness. Distal femoral osteotomy is usually used in patients with knee deformity. CONCLUSION: For patients with Crowe type IV DDH complicated by severe femoral dislocation and soft tissue spasm, subtrochanteric osteotomy should be selected, whereas it needs an associated standard focusing on how to select the osteotomy shape and length in subtrochanteric ostetomy, which needs an advanced research.

Gelfoam embolization or 125I seed implantation may be a more effective treatment than surgical treatment for giant benign sacral neurogenic tumors.

BACKGROUND: The goal of the present study was to assess the effects of computed tomography (CT)-guided iodine-125 (125I) seed implantation or gelatin sponge particle (GSP) embolization on patients with giant benign sacral neurogenic tumors. METHODS: A total of 24 cases with giant sacral neurogenic tumor were performed in a retrospective study between 2000 and 2012. Nineteen cases received surgical resection, and five cases received non-surgical treatment. In surgical group, patients with type III sacral tumor had received a combined anterior-posterior approach and patients with type IV were treated with simple anterior approach. In non-surgical group, CT-guided 125I seed implantation or GSP embolization was applied to occlude vessels. Besides, CT scanning or magnetic resonance imaging was used to assess the size and development of tumors. RESULTS: Two of the five patients were treated three times with GSP embolization, one had received GSP embolization combined with CT-guided 125I seed implantation, one case did not receive any treatment, and one patient was lost to follow-up. Patients in non-surgical group were followed up for 2-8 years. CONCLUSIONS: Our study suggested that CT-guided 125I seed implantation or GSP embolization treatment is very useful to slow down the development of giant benign sacral neurogenic tumors.

Bioactive lipid coating of bone allografts directs engraftment and fate determination of bone marrow-derived cells in rat GFP chimeras.

Bone grafting procedures are performed to treat wounds incurred during wartime trauma, accidents, and tumor resections. Endogenous mechanisms of repair are often insufficient to ensure integration between host and donor bone and subsequent restoration of function. We investigated the role that bone marrow-derived cells play in bone regeneration and sought to increase their contributions by functionalizing bone allografts with bioactive lipid coatings. Polymer-coated allografts were used to locally deliver the immunomodulatory small molecule FTY720 in tibial defects created in rat bone marrow chimeras containing genetically-labeled bone marrow for monitoring cell origin and fate. Donor bone marrow contributed significantly to both myeloid and osteogenic cells in remodeling tissue surrounding allografts. FTY720 coatings altered the phenotype of immune cells two weeks post-injury, which was associated with increased vascularization and bone formation surrounding allografts. Consequently, degradable polymer coating strategies that deliver small molecule growth factors such as FTY720 represent a novel therapeutic strategy for harnessing endogenous bone marrow-derived progenitors and enhancing healing in load-bearing bone defects.

Inhibition of differentiation and function of osteoclasts by dimethyl sulfoxide (DMSO).

Dimethyl sulfoxide (DMSO) is an FDA-approved organosulfur solvent that is reported to have therapeutic value in osteoarthritis and osteopenia. DMSO is used as a cryoprotectant for the cryopreservation of bone grafts and mesenchymal stem cells which are later used for bone repair. It is also used as a solvent in the preparation of various scaffolds used for bone tissue engineering purposes. DMSO has been reported to inhibit osteoclast formation in vitro but the mechanism involved has remained elusive. We investigated the effect of DMSO on osteoclast differentiation and function using a conventional model system of RAW 264.7 cells. The differentiation of RAW 264.7 cells was induced by adding 50 ng/ml RANKL and the effect of DMSO (0.01 and 1% v/v) on RANKL-induced osteoclastogenesis was investigated. Addition of 1% DMSO significantly inhibited RANKL-induced formation of TRAP+, multinucleated, mature osteoclasts and osteoclast late-stage precursors (c-Kit(-) c-Fms(+) Mac-1(+) RANK(+)). While DMSO did not inhibit proliferation per se, it did inhibit the effect of RANKL on proliferation of RAW 264.7 cells. Key genes related to osteoclast function (TRAP, Integrin αVß3, Cathepsin K and MMP9) were significantly down-regulated by DMSO. RANKL-induced expression of RANK gene was significantly reduced in the presence of DMSO. Our data, and reports from other investigators, that DMSO enhances osteoblastic differentiation of mesenchymal stem cells and also prevents bone loss in ovarietcomized rats, suggest that DMSO has tremendous potential in the treatment of osteoporosis and bone diseases arising from uncontrolled activities of the osteoclasts.

Influences of continuous femoral nerve block on knee function and quality of life in patients following total knee arthroplasty.

OBJECTIVE: Continuous femoral nerve block (CFNB), guided by ultrasound combined nerve stimulations, offers advantages for both sides and provides effective postoperative analgesia after total knee arthroplasty (TKA). The objective of this study was to evaluate the medium-term impact of continuous femoral nerve block on knee function and quality of life in patients following TKA. METHODS: This was a follow-up study. Total 168 adult patients scheduled for elective TKA were randomly allocated to receive postoperative continuous femoral nerve block guided by ultrasound combined nerve stimulator (group CFNB, n = 82) or patient-controlled epidural analgesia (group PCEA, n = 86). Quality of life, knee function, patient satisfaction, pain medication and associated adverse effects were compared at 1, 3, 6, and 12 months postoperatively. Quality of life was assessed using the Medical Outcomes Study Short Form-36 Health Survey (MOS SF-36), and clinical results were assessed using the Hospital for Special Surgery (HSS) Knee Scoring System. Patient satisfaction scores were divided into four categories. RESULTS: A total of 162 patients completed the 12-month follow-up. The CFNB group patients had significantly improved SF-36 scores and physical function at 1 month postoperatively (P < 0.05); the remaining seven dimensions were similar between the two groups. No differences were observed at 3, 6 or 12 months. HSS scores for the four observational time points were comparable. The CFNB group patients reported less pain; improved knee function, maximum flexion and strength; less celecoxib consumption and fewer side effects at 1 month than the PCEA group patients. The satisfaction score at 12 months decreased significantly, compared with that at 1 month in both groups (3.6 to 2.95 and 3.4 to 2.45, respectively). No difference in satisfaction score was observed between the two groups. CONCLUSIONS: Continuous femoral nerve block not only could provide effective postoperative analgesia but also could improve joint function and quality of life in patients at one month postoperatively. Continuous femoral nerve block is a good choice for postoperative analgesia after TKA.

High extracellular magnesium inhibits mineralized matrix deposition and modulates intracellular calcium signaling in human bone marrow-derived mesenchymal stem cells.

Mesenchymal stem cells (MSCs) have the potential to differentiate into several cell types and provide an attractive source of autologous cells for regenerative medicine. However, their cellular biology is not fully understood. Similar to Ca(2+), extracellular Mg(2+) plays an important role in the functions of the skeletal system. Here, we examined the effects of extracellular Mg(2+) on the deposition of calcium phosphate matrix and Ca(2+) signaling with or without ATP stimulation in human bone marrow-derived mesenchymal stem cells (hBMSCs). We found that high extracellular Mg(2+) concentration ([Mg(2+)]e) inhibited extracellular matrix mineralization in hBMSCs in vitro. hBMSCs also produced a dose-dependent decrease in the frequency of calcium oscillations during [Mg(2+)]e elevation with a slight suppression on oscillation amplitude. In addition, spontaneous ATP release was inhibited under high [Mg(2+)]e levels and exogenous ATP addition stimulated oscillation reappear. Taken together, our results indicate that high [Mg(2+)]e modulates calcium oscillations via suppression of spontaneous ATP release and inactivates purinergic receptors, resulting in decreased extracellular mineralized matrix deposition in hBMSCs. Therefore, the high magnesium environment created by the rapid corrosion of Mg alloys may result in the dysfunction of calcium-dependent physiology processes and be disadvantageous to hBMSCs physiology.

[Case-control study on minimally invasive percutaneous new plate osteosynthesis applied in proximal humerus fractures in elder patients].

OBJECTIVE: To evaluate the clinical significance of minimally invasive percutaneous new plate osteosynthesis (MIPPO) applied in three and four-part fractures of proximal humerus in elder patients. METHODS: From June 2008 to December 2010, 98 old patients with three and four-part fractures of proximal humerus were treated with locking plate osteosynthesis. There were 43 males and 55 females with an average age of (71.3 +/- 6.2) years ranging from 65 to 84. Among them,47 cases were treated with minimally invasive percutaneous new plate osteosynthesis (MIPPO) through antrolateral transdeoltoid approach, and meanwhile 51 cases were treated with open reduction and internal fixation (ORIF) through a traditional deltopectoral approach. The operation time,blood loss,wound complications and hospital stay were recorded. The functional outcomes of the shoulder were assessed according to Constant score. RESULTS: Ninety-six patients were followed up for 13 to 42 months (averaged 18.1 months),and 2 patients died during the follow-up period. The mean blood loss of the MIPPO group was lower than that of the ORIF group by 125 ml (P < 0.05). There was no difference in the operation time between two groups. But the MIPPO group had a slightly shorter hospital stay than the ORIF group (P < 0.05). All the fractures united clinically and radiologically. The difference of the mean healing time between two groups was not significant. The mean Constant score at final follow-up of two groups had no statistic difference. But the rate of complication of the MIPPO group was lower than that of the ORIF group (P < 0.05). Only 1 case of the MIPPO group had axillary nerve paralysis post-operatively, but 4 cases had slack internal fixation and 2 cases had avascular necrosis of the humeral head in the ORIF group. CONCLUSION: The technique of percutaneous insertion combined new locking plate internal fixation has the advantages of less blood loss, rapid recovery, less vascular damage, lower risk of complications and so on. It can effectively treat the proximal humerus three-and four-part fractures, especially to elder patients with osteoporosis.